Acute Inflammatory Response in Osteoporotic Fracture Healing Augmented with Mechanical Stimulation is Regulated In Vivo through the p38-MAPK Pathway

Chow, Simon Kwoon‐Ho; Cui, Can; Cheng, Keith Yu-Kin; Chim, Yu Ning; Wang, Jinyu; Wong, Carissa Hing Wai; Ng, Ka Ying Bonnie; Wong, Ronald Man Yeung; Cheung, Wing-Hoi

doi:10.3390/ijms22168720

Cited by 11 publications

(10 citation statements)

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“…Another paper investigated the role of p38 MAPK signaling in macrophages during bone fracture healing [6]. The mechanical vibration used in this study to facilitate fracture repair did not affect the polarization from M1 to M2, but instead promoted differentiation into a specific subset of dendritic monocytes/macrophages with the ability to produce both inflammatory and anti-inflammatory cytokines, suggesting that this cellular subtype does not fit a conventional M1/M2 classification [6] (Figure 2B). Barbeck et al investigated the monocyte-macrophage cellular response to biomaterial used for bone implantation [5].…”

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confidence: 85%

“…The main result was that the pore size, the granule shape and the diameter of the biomaterial used have an influence on the degradation of the material mediated by macrophages, and these factors were important for the functionality in correlation with the process of osteoconductivity [5]. Another paper investigated the role of p38 MAPK signaling in macrophages during bone fracture healing [6]. The mechanical vibration used in this study to facilitate fracture repair did not affect the polarization from M1 to M2, but instead promoted differentiation into a specific subset of dendritic monocytes/macrophages with the ability to produce both inflammatory and anti-inflammatory cytokines, suggesting that this cellular subtype does not fit a conventional M1/M2 classification [6] (Figure 2B).…”

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confidence: 99%

“…(A) Degradation of biomaterial by Mφ depends on the consistency of the biomaterial itself [5]. (B) Mechanical vibration induced an intermediate Mφ phenotype in fracture healing[6]. (C) ERAP2 short form caused an inhibition of anti-inflammatory ativity of Renin Angiotensin System[7].…”

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confidence: 99%

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Macrophage Polarization: Learning to Manage It

Lampiasi

2022

IJMS

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Macrophage Polarization: Learning to Manage It

Lampiasi

2022

IJMS

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“…Cultured osteocyte-like cells were divided into five groups including CT, VT, KD, KD+VT, and Sb+VT, as in vivo part. The cells in VT groups received 20 minutes/day, five days/ week of vibration treatment using a vibration platform providing LMHFV at 35 Hz, 0.3 g. [41][42][43][44] Treatment lasted for three, seven, and 14 days before being harvested for assessments including immunocytochemical (ICC) staining and mineralized nodule staining. DMP1 knockdown in MLO-Y4 cell line.…”

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confidence: 99%

Osteocyte-specific dentin matrix protein 1

Chow

Wong

et al. 2022

Bone & Joint Research

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Aims There is an increasing concern of osteoporotic fractures in the ageing population. Low-magnitude high-frequency vibration (LMHFV) was shown to significantly enhance osteoporotic fracture healing through alteration of osteocyte lacuno-canalicular network (LCN). Dentin matrix protein 1 (DMP1) in osteocytes is known to be responsible for maintaining the LCN and mineralization. This study aimed to investigate the role of osteocyte-specific DMP1 during osteoporotic fracture healing augmented by LMHFV. Methods A metaphyseal fracture was created in the distal femur of ovariectomy-induced osteoporotic Sprague Dawley rats. Rats were randomized to five different groups: 1) DMP1 knockdown (KD), 2) DMP1 KD + vibration (VT), 3) Scramble + VT, 4) VT, and 5) control (CT), where KD was performed by injection of short hairpin RNA (shRNA) into marrow cavity; vibration treatment was conducted at 35 Hz, 0.3 g; 20 minutes/day, five days/week). Assessments included radiography, micro-CT, dynamic histomorphometry and immunohistochemistry on DMP1, sclerostin, E11, and fibroblast growth factor 23 (FGF23). In vitro, murine long bone osteocyte-Y4 (MLO-Y4) osteocyte-like cells were randomized as in vivo groupings. DMP1 KD was performed by transfecting cells with shRNA plasmid. Assessments included immunocytochemistry on osteocyte-specific markers as above, and mineralized nodule staining. Results Healing capacities in DMP1 KD groups were impaired. Results showed that DMP1 KD significantly abolished vibration-enhanced fracture healing at week 6. DMP1 KD significantly altered the expression of osteocyte-specific markers. The lower mineralization rate in DMP1 KD groups indicated that DMP1 knockdown was associated with poor fracture healing process. Conclusion The blockage of DMP1 would impair healing outcomes and negate LMHFV-induced enhancement on fracture healing. These findings reveal the importance of DMP1 in response to the mechanical signal during osteoporotic fracture healing. Cite this article: Bone Joint Res 2022;11(7):465–476.

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“…Cells, including stem cells of the musculoskeletal tissue, are sensitive to high-frequency, low-intensity mechanical signals. This sensitivity can be utilized for the targeted treatment of tissues and for stem cell expansion, differentiation, and biomaterial interaction in tissue engineering applications [ 45 , 46 , 47 ].…”

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Influence of 40 Hz and 100 Hz Vibration on SH-SY5Y Cells Growth and Differentiation—A Preliminary Study

et al. 2022

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(1) Background: A novel bioreactor platform of neuronal cell cultures using low-magnitude, low-frequency (LMLF) vibrational stimulation was designed to discover vibration influence and mimic the dynamic environment of the in vivo state. To better understand the impact of 40 Hz and 100 Hz vibration on cell differentiation, we join biotechnology and advanced medical technology to design the nano-vibration system. The influence of vibration on the development of nervous tissue on the selected cell line SH-SY5Y (experimental research model in Alzheimer’s and Parkinson’s) was investigated. (2) Methods: The vibration stimulation of cell differentiation and elongation of their neuritis were monitored. We measured how vibrations affect the morphology and differentiation of nerve cells in vitro. (3) Results: The highest average length of neurites was observed in response to the 40 Hz vibration on the collagen surface in the differentiating medium, but cells response did not increase with vibration frequency. Also, vibrations at a frequency of 40 Hz or 100 Hz did not affect the average density of neurites. 100 Hz vibration increased the neurites density significantly with time for cultures on collagen and non-collagen surfaces. The exposure of neuronal cells to 40 Hz and 100 Hz vibration enhanced cell differentiation. The 40 Hz vibration has the best impact on neuronal-like cell growth and differentiation. (4) Conclusions: The data demonstrated that exposure to neuronal cells to 40 Hz and 100 Hz vibration enhanced cell differentiation and proliferation. This positive impact of vibration can be used in tissue engineering and regenerative medicine. It is planned to optimize the processes and study its molecular mechanisms concerning carrying out the research.

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Acute Inflammatory Response in Osteoporotic Fracture Healing Augmented with Mechanical Stimulation is Regulated In Vivo through the p38-MAPK Pathway

Cited by 11 publications

References 58 publications

Macrophage Polarization: Learning to Manage It

Macrophage Polarization: Learning to Manage It

Osteocyte-specific dentin matrix protein 1

Influence of 40 Hz and 100 Hz Vibration on SH-SY5Y Cells Growth and Differentiation—A Preliminary Study

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